title: Microbead-based biomimetic synthetic neighbors enhance survival and function of rat pancreatic β-cells.
abstract: Diabetes is caused by the loss or dysfunction of insulin-secreting β-cells in the pancreas. β-cells reduce their mass and lose insulin-producing ability in vitro, likely due to insufficient cell-cell and cell-extracellular matrix (ECM) interactions as β-cells lose their native microenvironment. Herein, we built an ex-vivo cell microenvironment by culturing primary β-cells in direct contact with 'synthetic neighbors', cell-sized soft polymer microbeads that were modified with cell-cell signaling factors as well as components from pancreatic-tissue-specific ECMs. This biomimetic 3D microenvironment was able to promote native cell-cell and cell-ECM interactions. We obtained sustained maintenance of β-cell function in vitro enhanced cell viability from the few days usually observed in 2D culture to periods exceeding three weeks, with enhanced β-cell stability and insulin production. Our approach can be extended to create a general 3D culture platform for other cell types.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Samuel
authors.initials: S
authors.lastname: Lee
authors.forename: Minglin
authors.initials: M
authors.lastname: Ma
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Patrick
authors.initials: P
authors.lastname: Guye
authors.forename: James R
authors.initials: JR
authors.lastname: Pancoast
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Ron
authors.initials: R
authors.lastname: Weiss
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry; D018929:Cell Culture Techniques; D002470:Cell Survival; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D046210:Microfluidic Analytical Techniques; D008863:Microspheres; D009928:Organ Specificity / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats
chemical_list: D007328:Insulin; D011092:Polyethylene Glycols; D005947:Glucose